: This research proposal addresses physiological mechanisms and processes underlying the association between depression and cardiovascular disease. Human studies demonstrate a strong link between depression and coronary artery disease but have not progressed beyond correlational methods. The current proposal will examine the underlying mechanisms in depression and cardiovascular pathology by using a rodent model of depression (chronic mild stress) and a combination of behavioral, physiological, and pharmacological techniques. Rats will be exposed to chronic mild stress to induce the depression-associated sign of anhedonia (a reduced capacity to experience pleasure), and tested for cardiovascular impairments (Aim 1). Autonomic nervous system imbalance will be examined as a mechanism for the cardiovascular dysfunction (e.g., elevated heart rate and reduced heart rate variability) associated with the chronic mild stress model (Aim 2). In addition, central serotonin activity will be examined as a common pathophysiological factor underlying both depression and cardiovascular/autonomic dysfunction (Aim 3). This research will extend our knowledge of the interactions between psychological and physiological conditions, and possibly prompt the development of new treatments for patients with depression and/or cardiovascular disease.